This project delineates biochemical, chemical, and pharmacological properties of sigma receptors and ligands. Sigma ligands are examined for a modulation of the NMDA receptor complex-mediated learning processes. Learning capacities are evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, and the step-down passive avoidance and the elevated plus-maze test for long-term memory. PRE-084, a selective sigma ligand discovered at this laboratory, attenuate MK-801-induced impairment of memory processes in all three tests. These effects of PRE-084 are antagonized by a sigma receptor antagonist BMY-14802. Solubilized sigma receptors are partially purified using anion-exchange and hydrophobic interaction chromatographies. Throughout the chromatographic procedures, a chromophore with a strong absorbance at 415 nm co-migrates with sigma receptors. The result suggests that sigma receptors may have a close relationship with a chromophore. Further purification of the receptors is underway.